327 research outputs found

    An entropy maximising model for estimating trip matrices from traffic counts

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    The main objective of this research is to develop and test a technique for estimating trip matrices from traffic counts. After discussing conventional methods for obtaining trip matrices an analysis is made of the problem of estimating them from traffic counts: it is found that in general the problem is underspecified in the sense that there will be more than one trip matrix which, when loaded onto a network, may reproduce a set of observed counts. A review is made of some models put forward to estimate a trip table from volume counts, the majority of them based on a travel demand model. A new model is then developed by the author within an entropy maximising formalism. The model may be interpreted as producing the most likely trip matrix consistent with the information contained in the counts and a prior trip matrix if available. This model does not require counts on all links in the network, can make efficient use of outdated trip matrices and other information, and is fairly modest in computer requirements. The model is then tested against real data collected by the Transport and Road Research Laboratory in the central area of Reading. Considerable temporal variability was found in the sampled trip matrices. The matrices estimated by the model are not very close to the observed ones but their errors are in general within the daily variations of the sampled matrices. A number of tests on the sensitivity of the model to errors and availability of traffic counts and route choice models used are also reported. A technique has been developed to rank links according to their potential contribution to the improvement of an estimated trip matrix. This scheme may be used to select new counting sites. The availability of a reasonable prior estimate of the trip matrix considerably improves the accuracy of the origin-destination matrix generated by the model. Some suggestions for extensions and further research are presented towards the end of this work

    Minimising barriers to dental care in older people

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    <p>Abstract</p> <p>Background</p> <p>Older people are increasingly retaining their natural teeth but at higher risk of oral disease with resultant impact on their quality of life. Socially deprived people are more at risk of oral disease and yet less likely to take up care. Health organisations in England and Wales are exploring new ways to commission and provide dental care services in general and for vulnerable groups in particular. This study was undertaken to investigate barriers to dental care perceived by older people in socially deprived inner city area where uptake of care was low and identify methods for minimising barriers in older people in support of oral health.</p> <p>Methods</p> <p>A qualitative dual-methodological approach, utilising both focus groups and individual interviews, was used in this research. Participants, older people and carers of older people, were recruited using purposive sampling through day centres and community groups in the inner city boroughs of Lambeth, Southwark and Lewisham in South London. A topic guide was utilised to guide qualitative data collection. Informants' views were recorded on tape and in field notes. The data were transcribed and analysed using Framework Methodology.</p> <p>Results</p> <p>Thirty-nine older people and/or their carers participated in focus groups. Active barriers to dental care in older people fell into five main categories: cost, fear, availability, accessibility and characteristics of the dentist. Lack of perception of a need for dental care was a common 'passive barrier' amongst denture wearers in particular. The cost of dental treatment, fear of care and perceived availability of dental services emerged to influence significantly dental attendance. Minimising barriers involves three levels of action to be taken: individual actions (such as persistence in finding available care following identification of need), system changes (including reducing costs, improving information, ensuring appropriate timing and location of care, and good patient management) and societal issues (such as reducing isolation and loneliness). Older people appeared to place greater significance on system and societal change than personal action.</p> <p>Conclusion</p> <p>Older people living within the community in an inner city area where NHS dental care is available face barriers to dental care. Improving access to care involves actions at individual, societal and system level. The latter includes appropriate management of older people by clinicians, policy change to address NHS charges; consideration of when, where and how dental care is provided; and clear information for older people and their carers on available local dental services, dental charges and care pathways.</p

    Familial Alzheimer's Disease Mutations in PSEN1 Lead to Premature Human Stem Cell Neurogenesis

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    Mutations in presenilin 1 (PSEN1) or presenilin 2 (PSEN2), the catalytic subunit of Îł-secretase, cause familial Alzheimer’s disease (fAD). We hypothesized that mutations in PSEN1 reduce Notch signaling and alter neurogenesis. Expression data from developmental and adult neurogenesis show relative enrichment of Notch and Îł-secretase expression in stem cells, whereas expression of APP and ÎČ-secretase is enriched in neurons. We observe premature neurogenesis in fAD iPSCs harboring PSEN1 mutations using two orthogonal systems: cortical differentiation in 2D and cerebral organoid generation in 3D. This is partly driven by reduced Notch signaling. We extend these studies to adult hippocampal neurogenesis in mutation-confirmed postmortem tissue. fAD cases show mutation-specific effects and a trend toward reduced abundance of newborn neurons, supporting a premature aging phenotype. Altogether, these results support altered neurogenesis as a result of fAD mutations and suggest that neural stem cell biology is affected in aging and disease

    On the evolution of clustering of 24um-selected galaxies

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    This paper investigates the clustering properties of a complete sample of 1041 24um-selected sources brighter than F[24um]=400 uJy in the overlapping region between the SWIRE and UKIDSS UDS surveys. We have concentrated on the two (photometric) interval ranges z=[0.6-1.2] (low-z sample) and z>1.6 (high-z sample) as it is in these regions were we expect the mid-IR population to be dominated by intense dust-enshrouded activity such as star formation and black hole accretion. Investigations of the angular correlation function produce a correlation length are r0~15.9 Mpc for the high-z sample and r0~8.5 Mpc for the low-z one. Comparisons with physical models reveal that the high-z sources are exclusively associated with very massive (M>~10^{13} M_sun)haloes, comparable to those which locally host groups-to-clusters of galaxies, and are very common within such (rare) structures. Conversely, lower-z galaxies are found to reside in smaller halos (M_min~10^{12} M_sun) and to be very rare in such systems. While recent studies have determined a strong evolution of the 24um luminosity function between z~2 and z~0, they cannot provide information on the physical nature of such an evolution. Our clustering results instead indicate that this is due to the presence of different populations of objects inhabiting different structures, as active systems at z<~1.5 are found to be exclusively associated with low-mass galaxies, while very massive sources appear to have concluded their active phase before this epoch. Finally, we note that the small-scale clustering data seem to require steep profiles for the distribution of galaxies within their halos. This is suggestive of close encounters and/or mergers which could strongly favour both AGN and star-formation activity.Comment: 13 pages, 8 figures, to appear in MNRA

    A highly obscured and strongly clustered galaxy population discovered with the Spitzer Space Telescope

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    The ~800 optically unseen (R>25.5) 24mum-selected sources in the complete Spitzer First Look Survey sample (Fadda et al. 2006) with F[24mum]>0.35 mJy are found to be very strongly clustered. If, as indicated by several lines of circumstantial evidence, they are ultraluminous far-IR galaxies at z ~ [1.6-2.7], the amplitude of their spatial correlation function is very high. The associated comoving clustering length is estimated to be r_0=14.0_{-2.4}^{+2.1} Mpc, value which puts these sources amongst the most strongly clustered populations of our known universe. Their 8mum-24mum colours suggest that the AGN contribution dominates above F[24mum] ~ 0.8 mJy, consistent with earlier analyses. The properties of these objects (number counts, redshift distribution, clustering amplitude) are fully consistent with those of proto-spheroidal galaxies in the process of forming most of their stars and of growing their active nucleus, as described by the Granato et al. (2004) model. In particular, the inferred space density of such galaxies at z ~ 2 is much higher than what expected from most semi-analytic models. Matches of the observed projected correlation function w(\theta) with models derived within the so-called Halo Occupation Scenario show that these sources have to be hosted by haloes more massive than ~10^{13.4} M_\odot. This value is significantly higher than that for the typical galactic haloes hosting massive elliptical galaxies, suggesting a duration of the starburst phase of massive high-redshift dusty galaxies of T_B ~ 0.5 Gyr.Comment: 14 pages, 10 figures, minor revisions, to appear on MNRA

    The PEP survey: clustering of infrared-selected galaxies and structure formation at z~2 in the GOODS South

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    ABRIDGED-This paper presents the first direct estimate of the 3D clustering properties of far-infrared sources up to z~3. This has been possible thanks to the Pacs Evolutionary Probe (PEP) survey of the GOODS South field performed with the PACS instrument onboard the Herschel Satellite. An analysis of the two-point correlation function over the whole redshift range spanned by the data reports for the correlation length, r_0~6.3 Mpc and r_0~6.7 Mpc, respectively at 100um and 160um, corresponding to dark matter halo masses M>~10^{12.4} M_sun. Objects at z~2 instead seem to be more strongly clustered, with r_0~19 Mpc and r_0~17 Mpc in the two considered PACS channels. This dramatic increase of the correlation length between z~1 and z~2 is connected with the presence of a wide, M>~10^{14} M_sun, filamentary structure which includes more than 50% of the sources detected at z~2. An investigation of the properties of such sources indicates the possibility for boosted star-forming activity in those which reside within the overdense environment with respect of more isolated galaxies found in the same redshift range. Lastly, we also present our results on the evolution of the relationship between luminous and dark matter in star-forming galaxies between z~1 and z~2. We find that the increase of (average) stellar mass in galaxies between z~1 and z~2 is about a factor 10 lower than that of the dark matter haloes hosting such objects ([z~1]/[z~2] ~ 0.4 vs M_{halo}[z~1]/M_{halo}[z~2] ~ 0.04). Our findings agree with the evolutionary picture of downsizing whereby massive galaxies at z~2 were more actively forming stars than their z~1 counterparts, while at the same time contained a lower fraction of their mass in the form of luminous matter.Comment: 14 pages, 8 figures, MNRAS accepte

    Cell-free (RNA) and cell-associated (DNA) HIV-1 and postnatal transmission through breastfeeding

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    &lt;p&gt;Introduction - Transmission through breastfeeding remains important for mother-to-child transmission (MTCT) in resource-limited settings. We quantify the relationship between cell-free (RNA) and cell-associated (DNA) shedding of HIV-1 virus in breastmilk and the risk of postnatal HIV-1 transmission in the first 6 months postpartum.&lt;/p&gt; &lt;p&gt;Materials and Methods - Thirty-six HIV-positive mothers who transmitted HIV-1 by breastfeeding were matched to 36 non-transmitting HIV-1 infected mothers in a case-control study nested in a cohort of HIV-infected women. RNA and DNA were quantified in the same breastmilk sample taken at 6 weeks and 6 months. Cox regression analysis assessed the association between cell-free and cell-associated virus levels and risk of postnatal HIV-1 transmission.&lt;/p&gt; &lt;p&gt;Results - There were higher median levels of cell-free than cell-associated HIV-1 virus (per ml) in breastmilk at 6 weeks and 6 months. Multivariably, adjusting for antenatal CD4 count and maternal plasma viral load, at 6 weeks, each 10-fold increase in cell-free or cell-associated levels (per ml) was significantly associated with HIV-1 transmission but stronger for cell-associated than cell-free levels [2.47 (95% CI 1.33–4.59) vs. aHR 1.52 (95% CI, 1.17–1.96), respectively]. At 6 months, cell-free and cell-associated levels (per ml) in breastmilk remained significantly associated with HIV-1 transmission but was stronger for cell-free than cell-associated levels [aHR 2.53 (95% CI 1.64–3.92) vs. 1.73 (95% CI 0.94–3.19), respectively].&lt;/p&gt; &lt;p&gt;Conclusions - The findings suggest that cell-associated virus level (per ml) is more important for early postpartum HIV-1 transmission (at 6 weeks) than cell-free virus. As cell-associated virus levels have been consistently detected in breastmilk despite antiretroviral therapy, this highlights a potential challenge for resource-limited settings to achieve the UNAIDS goal for 2015 of eliminating vertical transmission. More studies would further knowledge on mechanisms of HIV-1 transmission and help develop more effective drugs during lactation.&lt;/p&gt

    Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort

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    Introduction: Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one Δ4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two Δ4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubule‐associated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD. Methods: The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotype‐tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del–In9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid ÎČ1–42 (AÎČ1–42), total tau (t‐tau), tau phosphorylated at epitopes 181 (p‐tau181), 199 (p‐tau199), and 231 (p‐tau231), and visinin‐like protein 1 (VILIP‐1). Results: Significant increases in t‐tau and p‐tau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype. Conclusions: These results indicate that MAPT haplotype‐tagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD
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